The Applicant has filed several co-pending applications relating to biosensors or biosensor systems. Biosensors usually allow for the detection of a given specific molecule within an analyte or fluid sample, wherein the amount of said molecule is typically small. Therefore, target particles, for example super-paramagnetic label beads, are used which bind to a specific binding site or spot only, if the molecules to be detected are present within the analyte or fluid sample. Alternatively, in an inhibition assay these molecules may inhibit the binding of these particles or beads to a sensor surface. One known technique to detect these label particles bound to the binding spots or binding surface is FTIR. Therein, light is coupled into the sample or sample volume at an angle at which total internal reflection can occur. If no particles are present close to the sample surface, the light is completely reflected. If, however, the label particles are bound to said surface, the condition of total internal reflection is violated, a portion of the light is scattered into the sample and thus the amount of light reflected by the surface is decreased. By measuring the intensity of the reflected light with an optical detector, it is possible to estimate the amount of particles or beads bound to the surface.
However, one drawback of FTIR is that FTIR systems work in such a way that the starting signal, i.e., the signal when no particles or beads are present close to the sensor surface, is high. Binding of beads to the surface will then decrease the initially high optical signal. Thus, the signal x of interest, namely the amount of beads close to the surface, is measured by way of (1-x), i.e., as a (small) change of an initially high or large signal. If the change of the signal x, is rather small compared to the total measured optical signal, i.e. (1-x), this may cause so-called “gain problems”, as the starting signal is large with respect to the signal of interest. It is therefore difficult to amplify the signal x, as the background signal (1-x) is amplified as well, which may result, e.g., in a nonlinear behaviour or even a saturation of the amplifiers, ADC's etc. Furthermore, this leads to a signal which is very sensitive to gain variations and noise, e.g. electronic noise.